Bio-orthogonal click reaction-enabled highly specific in situ cellularization of tissue engineering scaffolds

Hydrogels are an important class of biomaterials with the unique property of high‐water content in a crosslinked polymer network. In particular, chemically crosslinked hydrogels have made a great clinical impact in past years because of their desirable mechanical properties and tunability of structural and chemical properties. Various polymers and step‐growth crosslinking chemistries are harnessed for fabricating such covalently crosslinked hydrogels for translational research. However, selecting appropriate crosslinking chemistries and polymers for the intended clinical application is time‐consuming and challenging. It requires the integration of polymer chemistry knowledge with thoughtful crosslinking reaction design. This task becomes even more challenging when other factors such as the biological mechanisms of the pathology, practical administration routes, and regulatory requirements add additional constraints. In this review, key features of crosslinking chemistries and polymers commonly used for preparing translatable hydrogels are outlined and their performance in biological systems is summarized. The examples of effective polymer/crosslinking chemistry combinations that have yielded clinically approved hydrogel products are specifically highlighted. These hydrogel design parameters in the context of the regulatory process and clinical translation barriers, providing a guideline for the rational selection of polymer/crosslinking chemistry combinations to construct hydrogels with high translational potential are further considered.

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“…recently reported the development of a DBCO‐functionalized film which can capture azide‐modified cells in vivo. [ 189 ]…”

Section: Crosslinking Chemistrymentioning

confidence: 99%

Covalently Crosslinked Hydrogels via Step‐Growth Reactions: Crosslinking Chemistries, Polymers, and Clinical Impact

2021

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“…Tissue engineering provides conceptually new opportunities for regenerative medicine as an alternative to conventional surgical transplantation, which may suffer from immune and infectious responses [ 1 , 2 ]. It heavily relies on natural or synthetic biocompatible polymers serving as matrices (often referred to as scaffolds) imitating natural tissues [ 3 , 4 ].…”

Section: Introductionmentioning

confidence: 99%

“…Poly(lactic acid) (PLA), poly(glycolic acid) (PGA), poly(ε)caprolactone (PCL), and polyurethane (PU) have been applied for scaffold material production [ 3 , 15 ]. Among these, PCL has been reported as one of the most suitable and desired synthetic biodegradable polymers for production of scaffold materials with strong mechanical properties and biocompatibility, suitable for tissue engineering, drug delivery, and wound dressing [ 2 , 13 ].…”

Section: Introductionmentioning

confidence: 99%

The Effect of Ozone Treatment on the Physicochemical Properties and Biocompatibility of Electrospun Poly(ε)caprolactone Scaffolds

et al. 2021

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Ozonation has been proved as a viable surface modification technique providing certain properties to the scaffolds that are essential in tissue engineering. However, the ozone (O3) treatment of PCL scaffolds in aqueous environments has not yet been presented. O3 treatment performed in aqueous environments is more effective compared with traditional, executed in ambient air treatment due to more abundant production of hydroxyl radicals (•OH) within the O3 reaction with water molecules. During interaction with •OH, the scaffold acquires functional groups which improve wettability properties and encapsulate growth factors. In this study, a poly(ε)caprolactone (PCL) scaffold was fabricated using solution electrospinning and was subsequently ozonated in a water reactor. The O3 treatment resulted in the expected occurrence of oxygen-containing functional groups, which improved scaffold wettability by almost 27% and enhanced cell proliferation for up to 14 days. The PCL scaffold was able to withhold 120 min of O3 treatment, maintaining fibrous morphology and mechanical properties.

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“…Most examples of cell–polymer hybrids employing bioorthogonal chemistry have utilized SPAAC due to the facile, well-studied integration of azide moieties on the cell surface. − Additionally, cyclooctyne–azide interactions are not naturally found in biological systems, enabling superior control over the desired reaction that is not possible with other approaches like thiol-based ligations.…”

Section: Interfacing Bioorthogonal Click Chemistry With Living Systemsmentioning

confidence: 99%

“…The goal of this study was to develop multifunctional hydrogels with unique behavior related to the use of living cells as the cross-linker; proliferation of the cells was found to directly affect hydrogel swelling and degradation as a result of this linkage. Further, Mao et al used SPAAC between poly(ε-caprolactone) (PCL)/PEG polymers functionalized with DBCO moieties and azide-expressing macrophages to fabricate an electrospun, cellularized polymeric film . The cells remained viable and metabolically active, demonstrating that SPAAC can be successfully combined with electrospinning while maintaining cell–polymer interactions, with potential for use in tissue engineering and regenerative medicine.…”

Section: Interfacing Bioorthogonal Click Chemistry With Living Systemsmentioning

confidence: 99%

Recent Advances in Bioorthogonal Click Chemistry for Biomedical Applications

2022

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Bioorthogonal click chemistry, first introduced in the early 2000s, has become one of the most widely used approaches for designing advanced biomaterials for applications in tissue engineering and regenerative medicine, due to the selectivity and biocompatibility of the associated reactants and reaction conditions. In this review, we present recent advances in utilizing bioorthogonal click chemistry for the development of three-dimensional, biocompatible scaffolds and cell-encapsulated biomaterials. Additionally, we highlight recent examples using these approaches for biomedical applications including drug delivery, imaging, and cell therapy and discuss their potential as next generation biomaterials.

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Bio-orthogonal click reaction-enabled highly specific in situ cellularization of tissue engineering scaffolds

Cited by 22 publications

References 32 publications

Covalently Crosslinked Hydrogels via Step‐Growth Reactions: Crosslinking Chemistries, Polymers, and Clinical Impact

Covalently Crosslinked Hydrogels via Step‐Growth Reactions: Crosslinking Chemistries, Polymers, and Clinical Impact

The Effect of Ozone Treatment on the Physicochemical Properties and Biocompatibility of Electrospun Poly(ε)caprolactone Scaffolds

Recent Advances in Bioorthogonal Click Chemistry for Biomedical Applications

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